A wide variety of products are currently available in the medical field for use as dressings in treating surgical incisions, abrasions, and burns, and as an aid in the treatment of a variety of dermatological skin disorders. Plain and medicated gauze-type dressings are widely employed in hospitals after major surgery and also in the home for minor accidental injuries. However, in spite of their wide acceptance, the gauze-type dressings are not without their disadvantages. For instance, frequent changes of such dressings are necessary in order to observe the healing process and to apply medication. Such changes are often accompanied by discomfort to the patient since some adherence to the wound or wound exudate normally occurs. Moreover, the gauze-type dressings do not protect the wound from extraneous bacteria nor do they control the proper moisture balance favorable to healing.
More recently, various polymeric materials have been investigated for use in the treatment of wounds, burns, and other skin disorders. For example, collagen, polyvinyl alcohol, gelatin, and a wide variety of polymeric materials have been disclosed in the literature as being useful in the treatment of accidental and surgical wounds. Hydrophilic polymer gels of polyethylene oxide and their use as wound dressings are described in U.S. Pat. No. 3,419,006 and suggested to be particularly useful in the treatment of burns, surgical and accidental injuries to the skin and eyes, and in a variety of dermatological applications. These gel dressings are alleged to provide a barrier to bacteria and viruses, to be permeable to vapors and gases while being impermeable to fluids, and to control the moisture environment of the wound.
Gauze pads wetted with physiologically acceptable fluids such as glycerol have been suggested for use as tissue drapes to prevent exposed organs from surface drying during extended surgical procedures. Gauze pads impregnated with antibacterial aqents may be used as wipes to clean and disinfect or otherwise treat skin areas. Gauze, however, is not lint-free, and the deposition of lint on treated surfaces is considered undesirable in many situations.
The present invention relates to a liquid-loaded material useful as a wound dressing, surgical wipe, treatment pad, burn bandage, tissue/organ drape, and the like. Materials of the present invention comprise a pellicle of microbially-produced cellulose loaded with a physiologically-acceptable liquid and sterilized prior to use. One microbial agent particularly useful for preparing the dressings of the present invention is Acetobacter xylinum (A.x.). For purposes of understanding the present invention, the following is a brief description of the mechanism of cellulose production by A.x.
Acetobacter xylinum is a widely distributed, aerobic, gram-negative bacterium which converts glucose to cellulose and which can be found occurring naturally in fermenting sweet plant juices or rotting sugary fruits or vegetables. The naturally occurring A.x. bacteria includes mixtures of strains which vary in degree of cellulose producing efficiency. Bacteriological selection of high growth cellulose-producing strains is possible, and purified strains of A.x. such as strain number ATCC 23769 are available from such sources such as the American Type Culture Collection.
Acetobacter xylinum has been studied by numerous investigators whose interests have centered mainly on its cellulose generating mechanism. The major underlying scientific impetus throughout previous years of study has been that an understanding of cellulose formation in the simpler A.x. (prokaryotic) system would provide improved insight into cellulose formation from eukaryotic cells (sources of cotton, wood or paper products). The A.x. cellulose generating mechanism, however, has proven sufficiently complex that its exact biochemical sequence has not yet been fully elucidated, even though major insights have been achieved recently into the mechanics of cellulose extrusion from A.x.
Acetobacter xylinum is a rod-shaped bacterium having approximate dimensions of 3 .mu.M.times.0.6 .mu.M. The linear extension rate for cellulose growth is on the order of 1-2.5 .mu.M/minute which corresponds to 1.5-3.5.times.10.sup.8 glucose units processed per cell hour. Arranged at the bacterial surface, external to the plasma membrane, are typically 46 stationary synthesis sites for cellulose. The sites are arranged in two closely spaced lines of 23 sites each, and this double row lies parallel with the long axis of the bacterium. The sites are about 120 .ANG.-150 .ANG. in diameter and 35 .ANG. in depth. Multiple poly-B-1,4-glucan chains (cellulose) issuing from each of the 46 sites combine to form individual microfibril ribbons about 1.6 nM.times.5.8 nM in cross section. Very near the bacterial surface, the 46 microfibrils assemble into a single fibril which lies parallel to the bacterial surface and grows outward from the end of the bacterium. Thus, one bacterium typically produces one fibril of cellulose about 3.2 nM.times.133 nM in cross section consisting of 46 microfibrils composed of multiple poly-B-1,4-glucan chains.
Extrusion of cellulose by A.x. is continuous and even occurs during cell division. The length of the cellulose fibril produced under ideal growing conditions is therefore limited only by the life span of the cellulose-producing bacteria. Fibril length can be controlled, however, by intermittent agitation of the growth medium. Still medium allows production of continuous fibril lengths while agitation breaks the bacterium away from the cellulose fibril at the 46 extrusion sites. Thus, intermittent agitation produces fibrils of finite length, which is determined by the linear extension rate and time between agitative shearing of the fibril from the bacterial surface.
Production of cellulose by A.x. typically involves bacterial activity at the air/liquid-medium interface. Each bacterium produces one fibril and the random intertwining of the fibrils results in a gelatinous, liquid-swollen structure known as a pellicle. Pellicle formation at the air/liquid interface is such that new cellulose is formed on top of existing cellulose, such that the existing cellulose is forced downward into the growth media. As a result, material placed lightly onto the liquid-medium surface becomes engulfed in pellicle and descends into the liquid-medium as more pellicle is formed. In this way, formation of cellulose pellicle is from the top down so that pellicle formation is analogous to formation of peat moss bog.
Cellulose fibrils formed by A.x. are much smaller than cellulose fibers from standard pulping of wood as seen from the following data:
______________________________________ Cellulose Fiber Dimensions Source Length Width ______________________________________ A.x. cellulose "infinite" 1.33 .times. 10.sup.-4 mm Birch 0.8-1.6 mm 1.4-4.0 .times. 10.sup.-2 mm Pine 2.6-4.4 mm 3.0-7.5 .times. 10.sup.-2 mm ______________________________________
It is accordingly an object of the present invention to provide a novel liquid loaded material for medical applications. A further object is to provide a wound dressing which is capable of cooling the skin surface and is accordingly particularly useful in the treatment of burns or other accidental injury to the skin surface. A still further object is to provide a novel treatment pad or wound dressing having one or more medicaments and/or additives incorporated therein. A still further object is to provide a wet sterile sheet-like material having exceptional strength and excellent handling and drape characteristics which allow the material to conform to the surface of the wound. A further object of the invention is to provide a novel dressing that can either supply moisture to the wound site or absorb exudate generated by the wound. A still further object of the present invention is to provide a process for the preparation of the aforementioned novel liquid loaded materials. These and other objects will readily become apparent to those skilled in the art in view of the teachings hereinafter set forth.